The principal long-term goal of this project is identification of the male-determining gene(s) on the human Y chromosome, and analysis of the structure and function of that gene or gene complex. Should this line of inquiry lead to identification of a putative male-determining gene, that gene or its mouse homolog will be introduced into mouse embryos to test its ability to induce testicular differentiation. These studies may result in a highly defined mouse model for the study of abnormal sexual development. The search for this male-determining gene will entail detailed study at the DNA level of the sex chromosomes of human sex reversal mutants (e.g., XX males and Xy females). The chromosomal basis of these sex reversal/infertility syndromes will thereby be elucidated. Regions of DNA sequence homology between the human X and Y chromosomes will be examined. In particular, the nature and evolutionary origin of substantial homologies between the short arm of the Y and the long arm of the X will be explored.